Mitigating breast cancer with a transdermal formulation of letrozole-loaded transbilosomes: in vitro and in vivo studies.

Design-Expert® Optimization of Tamoxifen-Loaded Transethosomal Gels: A Promising Transdermal System with Cytotoxicity and Stability Validation

Background: This study evaluates transdermal delivery of tamoxifen (TXN) as an alternative to the oral route of administration in treating breast cancer, which is the leading cause of cancer-related death in women globally. Oral TXN, a Class II drug, is associated with first-pass metabolism and serious side effects, including secondary cancers. Objectives: To enhance transdermal delivery, lipid-based transethosomes (TRS) were formulated using three different 24 factorial designs with various non-ionic surfactants, including Tween 20®, Span 20®, and Span 80®. Methods: Optimized TRS formulations were incorporated into HPMC-based gels and characterized for morphology, drug content, pH, viscosity, spreadability, ex vivo skin penetration, and deposition. Additionally, cytotoxicity and stability were assessed. Results: All TXN-TRS gels were suitable for transdermal use; however, Span 20®-based TRS gel demonstrated the highest skin penetration (40.3 ± 1.5 µg/cm2), representing a 127-fold enhancement rate compared with the non-ethosomal TXN gel. In line with the enhanced penetration profile, cellular studies on MCF-7 cells showed concentration-dependent cytotoxicity, reaching 91.24 ± 1.01% inhibition at 2% w/w after 72 h, with an IC50 value of 0.85 ± 0.02% w/w. Stability testing showed all formulations were more stable under refrigeration than at dry room temperature storage, supporting their potential as preclinical transdermal tamoxifen delivery platforms. Conclusions: Span 20®-based TXN transethosomal gel markedly enhanced skin penetration while maintaining potent cytotoxic activity, supporting its further preclinical evaluation as a promising transdermal alternative to oral tamoxifen.

Control of Skin Carcinoma via Sonidegib-loaded Transbilosomes.

The uncontrolled proliferation of abnormal skin cells is the hallmark of skin carcinoma. Sonidegib (SDB), a potent Hedgehog pathway inhibitor, is clinically approved for the treatment of skin carcinoma. However, its therapeutic utility is restricted by poor bioavailability, high hydrophobicity, and significant systemic adverse effects. This study aimed to develop an intratumor SDB-loaded transbilosomes (SLT) formulation to improve localized therapeutic efficacy and mitigate systemic toxicity. Several SLT formulations were developed and optimized using Design-Expert® software. The optimized SLT formulation was evaluated for safety, intratumor retention, and efficacy using a DMBA-induced skin carcinoma rat model. Results demonstrated that the optimal SLT formulation achieved a 68.87% reduction in drug release after 24 hours compared to free SDB. Pharmacokinetic evaluation revealed a 7.78-fold increase in relative systemic bioavailability compared to oral SDB. In vivo efficacy studies showed an 84.22% reduction in tumor volume in the intratumor SLT-treated group, with no observed fatalities compared to the oral SDB. Histopathological and safety assessments confirmed the significant antiproliferative effects and the favorable preliminary safety profile of the intratumor SLT formulation. These findings suggest that the intratumor SLT formulation provides an effective option for the management of skin carcinoma.

Liposomes-enabled gemcitabine therapy for breast cancer: in vitro and in vivo studies.

Soluplus®-based solid dispersion enhances oral bioavailability of A10: a cGAS-STING and ICD activator for bladder cancer therapy.

Bladder cancer (BCa) is one of the most prevalent malignancies worldwide, and the clinical treatment effect is limited due to the resistance and the associated low survival rates in patients. A10, as a novel camptothecin (CPT) derivative, possesses potent anti-tumor activity by targeting Topo Ⅰ/DDX5 (p68). However, the poor aqueous solubility and low bioavailability of A10 restrict its further application. We developed a Soluplus® - based solid dispersion (A10-SD) to enhance solubility by 389-fold and oral bioavailability by 14.38-fold. This research provided evidence of the immune activation induced by A10 against BCa T24 cells, and A10 could activate the cGAS-STING pathway, promote DAMPs release, and induce Immunogenic Cell Death (ICD) for anti-tumor activity against BCa cells in vitro. A10-SD meanwhile demonstrated remarkable tumor-suppressive efficacy in vivo with TGI of 99.84%, and its immune activation was preliminarily confirmed in vivo. A10-SD also showed good safety. This strategy provides an effective approach for the development of orally administered poorly soluble compounds, helping to unlock their therapeutic potential and promote their application.

PEGylated Lipidic Nanocapsules Encapsulating Olaparib for Breast Cancer Therapy: In Vitro and In Vivo Evaluation

Optimization and evaluation of curcumin-loaded zein microneedles for potential treatment of melanoma.

Treatment of melanoma is challenging due to limited bioavailability of chemotherapeutic drugs, side effects, and poor patient compliance with conventional intravenous administration. We evaluated the potential of synthesizing zein microneedles (ZMNs) using curcumin (Cur) as an anticancer model compound as a non-invasive approach for the local treatment of melanoma. A QbD approach was employed to create ZMNs with optimal mechanical strength and membrane penetrability, using zein as the matrix and PVP as a plasticizer at a concentration of 50% (w/v) and 20% (w/v), respectively. ZMNs loaded with Cur at 0.5% drug loading (Cur-ZMNs) demonstrated suitable mechanical properties, desirable membrane insertion, and sustained Cur release in vitro up to 76.17% over 24 h. Ex vivo permeation studies with excised porcine skin showed significantly higher permeation of Cur from Cur-ZMNs (59.75 %) when compared to free Cur (11%). Cur-ZMNs efficiently killed A375 melanoma cells and reduced cell viability by 44%, which was comparable to that of free Cur. The membrane damage of melanoma cells, measured by lactate dehydrogenase (LDH) assay, further supported the cytotoxic effect of Cur-ZMNs against treated cells, while showing no toxic effect against normal fibroblasts, indicating the potential of prepared Cur-ZMNs for effective treatment of melanoma.